Consejo Nacional de Investigaciones Científicas y Técnicas de la República Argentina, CONICET, Santa Fe, Argentina and Área de Biocoloides y Nanotecnología, Instituto de Tecnología de Alimentos, Facultad de Ingeniería Química, Universidad Nacional del Litoral (ITA-FIQ-UNL), 1 de Mayo 3250, Santa Fe, 3000, Argentina.
Centro de Química Inorgánica (CEQUINOR-CONICET-UNLP), Universidad Nacional de La Plata (UNLP), La Plata, Buenos Aires, Argentina.
Food Funct. 2020 Jul 22;11(7):6007-6019. doi: 10.1039/d0fo00299b.
Development of nanosupplements based on bioactive compound encapsulation and their incorporation into diet constitutes a field that is growing exponentially. Among flavonoids, chrysin (Chrys) shows high antitumor activity but its poor water solubility limits its applications. Bovine serum albumin nanoparticles (BSAnp) with sizes in the range of 13-28 nm were previously prepared by applying a heat-induced self-assembly method, and they were able to load Chrys. Hence, the aim of this study is to provide information about elaboration of Chrys nanosupplements considering the incidence of the freeze-drying process of Chrys-loaded and unloaded BSAnp systems on aqueous redispersibility and on the retention of their physicochemical properties as examined by DSC, turbidity and DLS measurements. In general, the physicochemical properties of Chrys-loaded BSAnp were retained after the freeze-drying process. The cytotoxic activity of the reconstituted powders was assayed on MCF-7 and MDA-MB-231 cell lines (as models of cancer cell lines) by using the MTT assay. Furthermore, the mechanism of cell death was researched by Annexin V-FITC flow cytometry. The apoptosis-mediated cytotoxicity was higher for Chrys-loaded BSAnp than for the BSAnp system. The greatest in vitro cytotoxic effect was observed for the smallest sized Chrys-loaded BSAnp, which was obtained at pH 11.0 and 70 °C. Finally, this system was subjected to static in vitro gastrointestinal digestion using the standardized protocol, and ∼14% Chrys was released from BSAnp after digestion. These results would provide a procedure to obtain bioactive nanosupplements in a soluble form, and they would suggest that smaller sized Chrys-loaded BSAnp could be a promising oral delivery system for potential cancer therapies.
基于生物活性化合物包封的纳米补品的开发及其纳入饮食中构成了一个呈指数增长的领域。在类黄酮中，白杨素 (Chrys) 具有很高的抗肿瘤活性，但它的水溶性差限制了其应用。先前应用热诱导自组装方法制备了大小在 13-28nm 范围内的牛血清白蛋白纳米粒子 (BSAnp)，并且它们能够负载 Chry。因此，本研究的目的是提供有关 Chry 纳米补品的信息，考虑到 Chry 负载和未负载 BSAnp 系统的冷冻干燥过程对水再分散性以及通过 DSC、浊度和 DLS 测量保留其物理化学性质的影响。一般来说，冷冻干燥过程后 Chry 负载 BSAnp 的物理化学性质得以保留。通过 MTT 测定法，在用 MCF-7 和 MDA-MB-231 细胞系（作为癌细胞系模型）测定再配制粉末的细胞毒性活性。此外，通过 Annexin V-FITC 流式细胞术研究了细胞死亡的机制。与 BSAnp 系统相比，负载 Chry 的 BSAnp 介导的细胞毒性更高。在 pH 值为 11.0 和 70°C 时，获得了最小尺寸的 Chry 负载 BSAnp，其体外细胞毒性最大。最后，该系统采用标准化方案进行静态体外胃肠道消化，BSAnp 从 Chry 中释放约 14%。这些结果将提供一种获得可溶性生物活性纳米补品的方法，并表明较小尺寸的 Chry 负载 BSAnp 可能是一种有前途的口服癌症治疗药物递送系统。
